mTOR Modulates Lymphocyte Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis in Rats.

Na Cui; Long-xiang SU; Hao Wang; Meng Xiao; Fei Yang; Min Zheng; Xin LI; Ying-chun XU; Da-wei Liu

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mTOR Modulates Lymphocyte Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis in Rats.

Author: Na CUI ¹ ; Long-Xiang SU ¹ ; Hao WANG ¹ ; Meng XIAO ² ; Fei YANG ³ ; Min ZHENG ¹ ; Xin LI ¹ ; Ying-Chun XU ² ; Da-Wei LIU ¹
Author Information

1. Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
2. Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
3. Department of Critical Care Medicine, Chifeng Hospital, Chifeng, Inner Mongolia 024000, China.
Publication Type:Journal Article
MeSH: Animals; CD8-Positive T-Lymphocytes; cytology; metabolism; Cell Differentiation; genetics; physiology; Invasive Pulmonary Aspergillosis; metabolism; pathology; Lung; metabolism; pathology; Lymphocytes; cytology; immunology; Male; Rats; Rats, Wistar; T-Box Domain Proteins; genetics; metabolism; TOR Serine-Threonine Kinases; genetics; metabolism; Tissue Culture Techniques
From: Chinese Medical Journal 2016;129(14):1704-1710
CountryChina
Language:English
Abstract:
BACKGROUNDAspergillosis infection is common in the patients with insufficient immunity. The role of mammalian target of rapamycin (mTOR), T-box expressed in T-cells (T-bet), and eomesodermin (EOMES) in mediating T lymphocytes differentiation in response to Aspergillus fumigatus infection in immunocompromised rats was investigated in this study.
METHODSInvasive pulmonary aspergillosis (IPA) of immunosuppressive twenty male rats were established and sacrificed at 24 h (n = 5), 48 h (n = 5), 72 h (n = 5), and 96 h (n = 5) after A. fumigatus infection. In addition, control (n = 5), cyclophosphamide (CTX) (n = 5), and aspergillosis (n = 5) group were also established the tissues and pathology of lung tissue was examined by hematoxylin and eosin staining. CD8+ T-cells was sorted by flow cytometry. Serum mTOR, S6K, T-bet, and EOMES were quantified by enzyme-linked immunosorbent assay.
RESULTSHistology of lung tissue indicated severe lung tissue injury including infiltration of inflammatory cells, alveolar wall damage or degradation, blood congestion, and hemorrhage in the CTX, IPA, and CTX + IPA rats. Hyphae were seen in the IPA, and CTX + IPA groups. The proportion of CD8+ T-cells was significantly increased in the animals of CTX + IPA. Memory CD8+ T-cells was significantly increased in early stage (24 h and 48 h, P < 0.001), but decreased in the late phase of fungal infection (72 h and 96 h) in the animals of CTX + IPA. In addition, at early stage of fungal infection (24 h and 48 h), serum mTOR (P < 0.001), S6K (P < 0.001), and T-bet (P < 0.05) was significantly higher, while EOMES was significantly lower (P < 0.001), in CTX + IPA group than that in control, CTX alone or IPA alone group. Conversely, serum mTOR, S6K, T-bet, and EOMES showed opposite changed in the late stage (72 h and 96 h). Pearson's correlation analysis indicated that mTOR and S6K were significantly correlated with T-bet (r = 0.901 and 0.91, respectively, P < 0.001), but negatively and significantly correlated with EOMES (r = -0.758 and -0.751, respectively, P < 0.001).
CONCLUSIONSmTOR may regulate transcription factors of EOMES and T-bet, and by which mechanism, it may modulate lymphocytes differentiation in animals with immune suppression and fungal infection.